PBPath Journal Watch Articles

Wellcome to the PBPath Journal Watch!

This bi-monthly journal watch features exciting recently published pancreas and biliary pathology articles that will provide up to date medical knowledge in our field. These articles will be showcased in several convenient categories, including surgical pathology, molecular pathology and cytopathology among others. The articles in each category are in no particular order.

Previous months’ issues may be found in our archive.

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We hope that you will enjoy the new PBPath Journal Watch!

Surgical Pathology


Morphology, Diagnostics, IHC

Morphology, Diagnostics, IHC

  • Pancreatic cancer arising in the remnant pancreas is not always a relapse of the preceding primary



- Epidermoid cyst in intrapancreatic accessory spleen: A systematic review

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2018 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30366677

BACKGROUND/OBJECTIVES: Due to its rarity, epidermoid cyst in intrapancreatic accessory spleen (ECIPAS) is still a diagnostic dilemma during clinical practice. The aim of this review was to summarize the epidemiologic features and management of ECIPAS. METHODS: MEDLINE and EMBASE were searched for English articles reporting on ECIPAS up to April 30th, 2018 following the methodology suggested by the PRISMA guidelines. Categorical variables were reported as frequency and percentage. Continuous variables were reported as median (range). RESULTS: A total of 56 patients from 47 full articles were included for the final data synthesis. More than half of the ECIPASs (59%) were found incidentally. The female/male ratio was 1.33. ECIPAS is typically a single mono-/multi-lobular cystic lesions in the pancreatic tail with thickened cystic wall or various amount of solid component which had identical density/signal to the spleen on imaging examinations. The cyst is filled with serous or non-serous fluid. Recognition of the surrounding ectopic splenic tissue is the key point to diagnose ECIPAS. However, no preoperative examination was able to make a definite diagnosis. Almost all the patients (96%) received surgical treatment, due to the suspicion of pancreatic malignant or potentially malignant cystic tumor, especially mucinous cystic neoplasm (MCN). CONCLUSIONS: Although seldom encountered, ECIPAS should be considered as a differential diagnosis for pancreatic cystic lesions, especially when solid component was detected. As a benign disease, unnecessary surgery should be avoided. Because it is difficult to make a definite diagnosis preoperatively by one single examination, multiple modalities may be required.

- Pancreatic extragastrointestinal stromal tumor invading the duodenum

Turkish journal of surgery 2018 01;34(3):231-233

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30302427

Extragastrointestinal stromal tumors that arise in the pancreas are extremely rare and managing them can be difficult, particularly if located in the head of pancreas. This case report aims to contribute to the existing data in the literature regarding extragastrointestinal stromal tumors with rare and unusual locations. We present a 56-year-old man who presented with recurrent mild right upper quadrant abdominal pain. Abdominal computed tomography and magnetic resonance imaging revealed a mass lesion with a diameter of 10 cm localized in the head of pancreas. Pancreaticoduodenectomy with complete tumor excision was performed. He was discharged on the postoperative day 14. Only 15 extragastrointestinal stromal tumors cases have been reported. Of these 15 cases, tumors were located in the head of pancreas in six cases. Here we report the seventh case of pancreatic extragastrointestinal stromal tumor arising in the head of pancreas and also the largest of these seven tumors.

- The expression of death receptor systems TRAIL-R1/-R2/-R4, CD95 and TNF-R1 and their cognate ligands in pancreatic ductal adenocarcinoma

Histology and histopathology 2018 Oct;():18054

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30375637

The expression of five members of the TNF receptor superfamily and two of their ligands in human pancreatic ductal adenocarcinoma were investigated in parallel by immunohistochemistry. 41 patients with histologically confirmed ductal carcinoma of the pancreas were enrolled in this study in order (i) to compare the individual TNFR-SF expression and their ligands in PDAC-cells and (ii) to investigate their correlation with survival data. All patients had undergone pancreaticoduodenectomy and were staged as pT3N1M0. Immunostaining was done on FFPE tissue sections of the tumor tissue, using antibodies directed against TRAIL-Receptor-1, -2 and -4, TRAIL, CD95, TNF-Receptor-1 and TNF-α. The intensity and quantity of immunostaining were evaluated separately for tumor cell cytoplasm and tumor cell nucleus. Immunostaining results were correlated with each other and with patient survival. All proteins were found to be expressed in the majority of the tumor cells. The expression (i) of the following members of TNFR-SF and their ligands correlated with each other: TNF-Receptor-1 and TNFα (cytoplasmatic scores, p=0.001), TNF-Receptor 1 and TRAIL (nuclear antigen expression p=0.005 and the main score p=0.001, which contains the overall intracellular antigen expression), TNF-Receptor 1 and CD95 (main score, p=0.001), TRAIL-Receptor-1 and TRAIL-Receptor-2 (nuclear parameters, p=0.023), TRAIL-Receptor-4 and TRAIL (main score p=0.041). In addition (ii), high cytoplasmatic expression of TNF-Receptor-1 and a strong cytoplasmatic and nuclear expression of CD95 correlated significantly with a better prognosis of the PDAC patients.

- Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer

British journal of cancer 2018 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30377341

BACKGROUND: Pancreatic cancer (PC) hijacks innate cellular processes to promote cancer growth. We hypothesized that PC exploits PD-1/PD-L1 not only to avoid immune responses, but to directly enhance growth. We also hypothesized that immune checkpoint inhibitors (ICIs) have direct cytotoxicity in PC. We sought to elucidate therapeutic targeting of PD-1/PD-L1. METHODS: PD-1 was assessed in PC cells, patient-derived organoids (PDOs), and clinical tissues. Then, PC cells were exposed to PD-L1 to evaluate proliferation. To test PD-1/PD-L1 signaling, cells were exposed to PD-L1 and MAPK was examined. Radio-immunoconjugates with anti-PD-1 drugs were developed to test uptake in patient-derived tumor xenografts (PDTXs). Next, PD-1 function was assessed by xenografting PD-1-knockdown cells. Finally, PC models were exposed to ICIs. RESULTS: PD-1 expression was demonstrated in PCs. PD-L1 exposure increased proliferation and activated MAPK. Imaging PDTXs revealed uptake of radio-immunoconjugates. PD-1 knockdown in vivo revealed 67% smaller volumes than controls. Finally, ICI treatment of both PDOs/PDTXs demonstrated cytotoxicity and anti-MEK1/2 combined with anti-PD-1 drugs produced highest cytotoxicity in PDOs/PDTXs. CONCLUSIONS: Our data reveal PCs innately express PD-1 and activate druggable oncogenic pathways supporting PDAC growth. Strategies directly targeting PC with novel ICI regimens may work with adaptive immune responses for optimal cytotoxicity.

  • High nuclear Survivin expression as a poor prognostic marker in pancreatic ductal adenocarcinoma


  • Epidermoid cyst in intrapancreatic accessory spleen: A systematic review


  • Residual Tumor Index: A Prognostically Significant Pathologic Parameter in Neoadjuvant-treated Pancreatic Ductal Adenocarcinoma


  • Overexpression of folate receptor alpha is an independent prognostic factor for outcomes of pancreatic cancer patients


  • Solitary pancreatic metastasis of extremity myxoid liposarcoma: a case report and literature review


- PD-L1 expression in pancreatic adenosquamous carcinoma: PD-L1 expression is limited to the squamous component

Pathology, research and practice 2018 Dec;214(12):2069-2074

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30477643

AIM: We examined the programmed death-ligand 1 (PD-L1) expression in surgically resected pancreatic adenosquamous carcinoma (PASC) samples. Furthermore, the detection rate was also assessed using biopsy cases obtained from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). METHODS: Fifteen cases of PASC (six resected and nine EUS-FNA biopsied) from the Kurume University Hospital between 2009 and 2016 were used for the evaluation of PD-L1 expression. As a control group, 34 cases of pancreatic ductal adenocarcinomas (PDACs) were selected. To compare the positivity and intensity of PD-L1, two types of clones (SP263, E1L3N) were examined for immunostaining. Only the membrane expression of PD-L1 was regarded as positive. The PD-L1 expressions in the squamous cell carcinoma component (SCc), adenocarcinoma component (ACc), and immune cells were assessed separately. The ratio of PD-L1 expression was calculated by counting the positive tumor cells, and tumor proportion score (TPS) was applied (TPS; Null < 1%, low expression; 1 ≤ TPS ≤ 49% and high expression; ≥ 50%). RESULTS: PD-L1 expression was observed in five surgical PASC samples (83%). This shows that SCc presented a high expression in these cases. However, the overall TPS indicated a low expression. In contrast, only one case (3%) was positive for PD-L1 in PDACs, and the TPS indicated a low expression. No differences in PD-L1 expression were observed between the two clones, SP263 and E1L3N. High PD-L1 expression in the EUS-FNA sample was found in only one case (11%). DISCUSSION: Although assessment using the tumor cells of PASC samples obtained from EUS-FNA was difficult, this study suggests the selective expression of PD-L1 in the SCc of PASC. Furthermore, it was considered that immune checkpoint inhibitors could provide therapeutic effects selectively on the SCc for the entire range of TPSs, though the PD-L1 expression was low.

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Pancreas TNM staging, Margins, Survival

- ASO Author Reflections: Even in Pancreatic Cancer, not all N Diseases are Created Equal

Annals of surgical oncology 2018 Oct;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30284129

- International Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients With Resected Pancreatic Cancer

JAMA surgery 2018 Oct;():e183617

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=30285076

Importance: The recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation. Objective: To validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018. Exposures: Patients were retrospectively staged according to the seventh and eighth editions of the TNM staging system. Main Outcomes and Measures: Prognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics. Results: A total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition. Conclusions and Relevance: The eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.